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Mammalian protein arginine methyltransferase 7 (PRMT7) specifically targets R‐X‐R sites in lysine and arginine‐rich regions (555.1)
Author(s) -
Feng You,
Clarke Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.555.1
Subject(s) - arginine , protein arginine methyltransferase 5 , methylation , methyltransferase , histone , biochemistry , lysine , protein methylation , biology , histone methyltransferase , enzyme , histone h4 , rna splicing , chemistry , dna , microbiology and biotechnology , amino acid , rna , gene
The mammalian protein arginine methyltransferase 7 (PRMT7) has been implicated in roles of transcriptional regulation, DNA damage repair, RNA splicing, cell differentiation and metastasis. However, the type of reaction that it catalyzes and its substrate specificity remains controversial. In this study, we purified a recombinant mouse PRMT7 expressed in insect cells that demonstrates a robust methyltransferase activity. Using a variety of substrates, we demonstrate that the enzyme only catalyzes the formation of ω‐monomethylarginine residues and confirm its activity as the prototype type III PRMT. This enzyme is active on all recombinant human core histones, but histone H2B is a highly preferred substrate. Analysis of the specific methylation sites within intact histone H2B and within H2B and H4 peptides revealed novel post‐translational modification sites and a unique specificity of PRMT7 for methylating arginine residues in lysine‐ and arginine‐rich regions. We demonstrate that a prominent substrate recognition motif consists of a pair of arginine residues separated by one residue (R‐X‐R motif). These findings will significantly accelerate substrate profile analysis, biological function study, and inhibitor discovery for PRMT7. Grant Funding Source : Supported by NIH R01GM026020